王剑-遗传性心脏疾病的基因诊断与遗传咨询.pdfVIP

上海交通大学医学院附属 遗传性心脏疾病的基因 诊断与遗传咨询 上海交通大学医学院附属 上海儿童医学中心 王剑 遗传性心脏疾病  先天性心脏病 (Congenital Heart Defects,CHD)  遗传性心肌病 (Inherited Cardiomyopathy)  遗传性心律失常 (Inherited arrhythmia disorders) 或离子通道病 (Channelopathies)  其他：肺动脉高压(Pulmonary arterial hypertension)、 马凡氏综合征 …… 第一部分：先天性心脏病 (Congenital Heart Defects,CHD) Congenital Heart Defects (CHD) ： Epidemiology • 8-10/1,000 births • CHD account for: – 25% of all congenital malformations – 15% of all infant deaths • 20% with one CHD will have a second • 25% will have a second malformation – 骨骼肌肉疾病 (9%) – 中枢神经系统疾病 (8%) – 尿路 或肾脏 (5%) – 消化道 (4%) – 腭裂 (1.8%) CHD: 再发风险 （recurrence risk ） • Isolated(单纯性) CHD: – Risk of second affected child 1-6% • Parent with isolated CHD: – Risk of affected child up to 12% (higher if mother vs. father with CHD) • Recurrence risk doubles if two first degree relatives • Autosomal dominant syndrome: – 50% recurrence risk • Autosomal recessive syndrome: – 25% recurrence risk Non-syndromic CHD: 再发风险 （recurrence risk ） World J Cardiol. 2016 Feb 26;8(2):180-91. Heart Development • Week 3: CV System begins to develop (Days 21-22: Cardiac contractions 收缩 begin) • Week 3-8: Formation of the heart and major vessels(血管) • Week 5-Term: development of the conduction(传导) system (Days 20-50: the most sensitive time for disturbances in formation of the CV system) Most CHD multifactorial : Genetic and Environmental CHD and Genetic • Isolated (65-70%) – Multifactorial inheritance • Component of syndrome (25-30%) – Single gene , Copy Number Variants or chromosomal Aneuploidy(非整倍体) syndromes Down Syndrome • Phe